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Bin1 targeted immunotherapy alters the status of the enteric neurons and the microbiome during ulcerative colitis treatment

Ulcerative colitis (UC) is a common chronic disease of the large intestine. Current anti-inflammatory drugs prescribed to treat this disease have limited utility due to significant side-effects. Thus, immunotherapies for UC treatment are still sought. In the DSS mouse model of UC, we recently demons...

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Autores principales: Thomas, Sunil, Mercogliano, Giancarlo, Prendergast, George C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9629549/
https://www.ncbi.nlm.nih.gov/pubmed/36322599
http://dx.doi.org/10.1371/journal.pone.0276910
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author Thomas, Sunil
Mercogliano, Giancarlo
Prendergast, George C.
author_facet Thomas, Sunil
Mercogliano, Giancarlo
Prendergast, George C.
author_sort Thomas, Sunil
collection PubMed
description Ulcerative colitis (UC) is a common chronic disease of the large intestine. Current anti-inflammatory drugs prescribed to treat this disease have limited utility due to significant side-effects. Thus, immunotherapies for UC treatment are still sought. In the DSS mouse model of UC, we recently demonstrated that systemic administration of the Bin1 monoclonal antibody 99D (Bin1 mAb) developed in our laboratory was sufficient to reinforce intestinal barrier function and preserve an intact colonic mucosa, compared to control subjects which displayed severe mucosal lesions, high-level neutrophil and lymphocyte infiltration of mucosal and submucosal areas, and loss of crypts. A dysbiotic microbiome may lead to UC. We determined the effects of Bin1 mAb on the gut microbiome and colonic neurons and correlated the benefits of immunotherapeutic treatment. In the DSS model, we found that induction of UC was associated with disintegration of enteric neurons and elevated levels of glial cells, which translocated to the muscularis at distinct sites. Further, we characterized an altered gut microbiome in DSS treated mice associated with pathogenic proinflammatory characters. Both of these features of UC induction were normalized by Bin1 mAb treatment. With regard to microbiome changes, we observed in particular, increase in Enterobacteriaceae; whereas Firmicutes were eliminated by UC induction and Bin1 mAb treatment restored this phylum including the genus Lactobacillus. Overall, our findings suggest that the intestinal barrier function restored by Bin1 immunotherapy in the DSS model of UC is associated with an improvement in the gut microbiome and preservation of enteric neurons, contributing overall to a healthy intestinal tract.
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spelling pubmed-96295492022-11-03 Bin1 targeted immunotherapy alters the status of the enteric neurons and the microbiome during ulcerative colitis treatment Thomas, Sunil Mercogliano, Giancarlo Prendergast, George C. PLoS One Research Article Ulcerative colitis (UC) is a common chronic disease of the large intestine. Current anti-inflammatory drugs prescribed to treat this disease have limited utility due to significant side-effects. Thus, immunotherapies for UC treatment are still sought. In the DSS mouse model of UC, we recently demonstrated that systemic administration of the Bin1 monoclonal antibody 99D (Bin1 mAb) developed in our laboratory was sufficient to reinforce intestinal barrier function and preserve an intact colonic mucosa, compared to control subjects which displayed severe mucosal lesions, high-level neutrophil and lymphocyte infiltration of mucosal and submucosal areas, and loss of crypts. A dysbiotic microbiome may lead to UC. We determined the effects of Bin1 mAb on the gut microbiome and colonic neurons and correlated the benefits of immunotherapeutic treatment. In the DSS model, we found that induction of UC was associated with disintegration of enteric neurons and elevated levels of glial cells, which translocated to the muscularis at distinct sites. Further, we characterized an altered gut microbiome in DSS treated mice associated with pathogenic proinflammatory characters. Both of these features of UC induction were normalized by Bin1 mAb treatment. With regard to microbiome changes, we observed in particular, increase in Enterobacteriaceae; whereas Firmicutes were eliminated by UC induction and Bin1 mAb treatment restored this phylum including the genus Lactobacillus. Overall, our findings suggest that the intestinal barrier function restored by Bin1 immunotherapy in the DSS model of UC is associated with an improvement in the gut microbiome and preservation of enteric neurons, contributing overall to a healthy intestinal tract. Public Library of Science 2022-11-02 /pmc/articles/PMC9629549/ /pubmed/36322599 http://dx.doi.org/10.1371/journal.pone.0276910 Text en © 2022 Thomas et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Thomas, Sunil
Mercogliano, Giancarlo
Prendergast, George C.
Bin1 targeted immunotherapy alters the status of the enteric neurons and the microbiome during ulcerative colitis treatment
title Bin1 targeted immunotherapy alters the status of the enteric neurons and the microbiome during ulcerative colitis treatment
title_full Bin1 targeted immunotherapy alters the status of the enteric neurons and the microbiome during ulcerative colitis treatment
title_fullStr Bin1 targeted immunotherapy alters the status of the enteric neurons and the microbiome during ulcerative colitis treatment
title_full_unstemmed Bin1 targeted immunotherapy alters the status of the enteric neurons and the microbiome during ulcerative colitis treatment
title_short Bin1 targeted immunotherapy alters the status of the enteric neurons and the microbiome during ulcerative colitis treatment
title_sort bin1 targeted immunotherapy alters the status of the enteric neurons and the microbiome during ulcerative colitis treatment
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9629549/
https://www.ncbi.nlm.nih.gov/pubmed/36322599
http://dx.doi.org/10.1371/journal.pone.0276910
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